Showing papers by "St Bartholomew's Hospital published in 2013"

Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR Contrast Medium Safety Committee guidelines

Abstract: Purpose To update the guidelines of the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) on nephrogenic systemic fibrosis and gadolinium-based contrast media.

Analysis of colorectal cancers in British Bangladeshi identifies early onset, frequent mucinous histotype and a high prevalence of RBFOX1 deletion

Abstract: Background: Prevalence of colorectal cancer (CRC) in the British Bangladeshi population (BAN) is low compared to British Caucasians (CAU). Genetic background may influence mutations and disease features. Methods: We characterized the clinicopathological features of BAN CRCs and interrogated their genomes using mutation profiling and high-density single nucleotide polymorphism (SNP) arrays and compared findings to CAU CRCs. Results: Age of onset of BAN CRC was significantly lower than for CAU patients (p=3.0 x 10 -5 ) and this difference was not due to Lynch syndrome or the polyposis syndromes. KRAS mutations in BAN microsatellite stable (MSS) CRCs were comparatively rare (5.4%) compared to CAU MSS CRCs (25%; p=0.04), which correlates with the high percentage of mucinous histotype observed (31%) in the BAN samples. No BRAF mutations was seen in our BAN MSS CRCs (CAU CRCs, 12%; p=0.08). Array data revealed similar patterns of gains (chromosome 7 and 8q), losses (8p, 17p and 18q) and LOH (4q, 17p and 18q) in BAN and CAU CRCs. A small deletion on chromosome 16p13.2 involving the alternative splicing factor RBFOX1 only was found in significantly more BAN (50%) than CAU CRCs (15%) cases (p=0.04). Focal deletions targeting the 5’ end of the gene were also identified. Novel RBFOX1 mutations were found in CRC cell lines and tumours; mRNA and protein expression was reduced in tumours. Conclusions: KRAS mutations were rare in BAN MSS CRC and a mucinous histotype common. Loss of RBFOX1 may explain the anomalous splicing activity associated with CRC.

A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis

Abstract: Central neuropathic pain (CNP) occurs in many multiple sclerosis (MS) patients. The provision of adequate pain relief to these patients can very difficult. Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (USAN name, nabiximols; Sativex, GW Pharmaceuticals, Salisbury, Wiltshire, UK), to alleviate CNP. Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment, in a double-blind manner, for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain. This parallel-group phase of the study was then followed by an 18-week randomized-withdrawal study (14-week open-label treatment period plus a double-blind 4-week randomized-withdrawal phase) to investigate time to treatment failure and show maintenance of efficacy. A total of 339 patients were randomized to phase A (167 received THC/CBD spray and 172 received placebo). Of those who completed phase A, 58 entered the randomized-withdrawal phase. The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met, with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo (p = 0.234). However, an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point (p = 0.046). During the randomized-withdrawal phase, the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray, with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group (p = 0.04). The mean change from baseline in Pain Numerical Rating Scale (NRS) (p = 0.028) and sleep quality NRS (p = 0.015) scores, both secondary endpoints in phase B, were also statistically significant compared to placebo, with estimated treatment differences of −0.79 and 0.99 points, respectively, in favor of THC/CBD spray treatment. The results of the current investigation were equivocal, with conflicting findings in the two phases of the study. While there were a large proportion of responders to THC/CBD spray treatment during the phase A double-blind period, the primary endpoint was not met due to a similarly large number of placebo responders. In contrast, there was a marked effect in phase B of the study, with an increased time to treatment failure in the THC/CBD spray group compared to placebo. These findings suggest that further studies are required to explore the full potential of THC/CBD spray in these patients.

A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma.

Abstract: Bagnara, D., Kaufman, M.S., Calissano, C., Marsilio, S., Patten, P.E., Simone, R., Chum, P., Yan, X.J., Allen, S.L., Kolitz, J.E., Baskar, S., Rader, C., Mellstedt, H., Rabbani, H., Lee, A., Gregersen, P.K., Rai, K.R. & Chiorazzi, N. (2011) A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease. Blood, 117, 5463–5472. Brachtl, G., Sahakyan, K., Denk, U., Girbl, T., Alinger, B., Hofbauer, S.W., Neureiter, D., Hofbauer, J.P., Egle, A., Greil, R. & Hartmann, T.N. (2011) Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells. PLoS ONE, 6, e23758. Burger, J.A., Ghia, P., Rosenwald, A. & CaligarisCappio, F. (2009) The microenvironment in mature B-cell malignancies: a target for new treatment strategies. Blood, 114, 3367–3375. Hallaert, D.Y., Jaspers, A., van Noesel, C.J., van Oers, M.H., Kater, A.P. & Eldering, E. (2008) c-Abl kinase inhibitors overcome CD40-mediated drug resistance in CLL: implications for therapeutic targeting of chemoresistant niches. Blood, 112, 5141–5149. Hamilton, E., Pearce, L., Morgan, L., Robinson, S., Ware, V., Brennan, P., Thomas, N.S., Yallop, D., Devereux, S., Fegan, C., Buggins, A.G. & Pepper, C. (2012) Mimicking the tumour microenvironment: three different co-culture systems induce a similar phenotype but distinct proliferative signals in primary chronic lymphocytic leukaemia cells. British Journal of Haematology, 158, 589–599. Herishanu, Y., Perez-Galan, P., Liu, D., Biancotto, A., Pittaluga, S., Vire, B., Gibellini, F., Njuguna, N., Lee, E., Stennett, L., Raghavachari, N., Liu, P., McCoy, J.P., Raffeld, M., Stetler-Stevenson, M., Yuan, C., Sherry, R., Arthur, D.C., Maric, I., White, T., Marti, G.E., Munson, P., Wilson, W. H. & Wiestner, A. (2011) The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood, 117, 563–574. Hofbauer, J.P., Heyder, C., Denk, U., Kocher, T., Holler, C., Trapin, D., Asslaber, D., Tinhofer, I., Greil, R. & Egle, A. (2011) Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL. Leukemia, 25, 1452–1458. Messmer, B.T., Messmer, D., Allen, S.L., Kolitz, J. E., Kudalkar, P., Cesar, D., Murphy, E.J., Koduru, P., Ferrarini, M., Zupo, S., Cutrona, G., Damle, R.N., Wasil, T., Rai, K.R., Hellerstein, M.K. & Chiorazzi, N. (2005) In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest, 115, 755–764. Patten, P.E., Buggins, A.G., Richards, J., Wotherspoon, A., Salisbury, J., Mufti, G.J., Hamblin, T. J. & Devereux, S. (2008) CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment. Blood, 111, 5173–5181. Plander, M., Seegers, S., Ugocsai, P., DiermeierDaucher, S., Ivanyi, J., Schmitz, G., Hofstadter, F., Schwarz, S., Orso, E., Knuchel, R. & Brockhoff, G. (2009) Different proliferative and survival capacity of CLL-cells in a newly established in vitro model for pseudofollicles. Leukemia, 23, 2118–2128.

Standardization of Gleason grading among 337 European pathologists

Abstract: Aims: The 2005 International Society of Urological Pathology (ISUP) modification of Gleason grading recommended that the highest grade should always be included in the Gleason score (GS) in prostate biopsies. We analysed the impact of this recommendation on reporting of GS 6 versus 7. Methods and results: Fifteen expert uropathologists reached two-thirds consensus on 15 prostate biopsies with GS 6–7 cancer. Eighty-five microphotographs were graded by 337 of 617 members of the European Network of Uropathology (ENUP), representing 19 countries. There was agreement between expert and majority member GS in 12 of 15 cases, while members upgraded in three cases. Among members and the expert consensus, a GS >6 was assigned by 64.5% and 60%, respectively. Mean member GS was higher than consensus GS in nine of 15 cases. A Gleason pattern (GP) 5 was reported by 0.3–5.6% in 10 cases. Agreement between consensus and member GS was 58.2–89.3% (mean 71.4%) in GS 6 cases and 46.3–63.8% (mean 56.4%) in GS 7 cases (P = 0.009). Conclusions: While undergrading of prostate cancer used to be prevalent, some now tend to overgrade. Minimum diagnostic criteria for GP 4 and 5 in biopsies need to be better defined. Image libraries reviewed by experts may be useful for standardization.

Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

Abstract: Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20+/CD22+ B-cell non-Hodgkin lymphoma (NHL). Patients and Methods A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles. Results In all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%)....

Low-dose phase contrast tomography with conventional x-ray sources

Abstract: Purpose: The edge illumination (EI) x-ray phase contrast imaging (XPCi) method has been recently further developed to perform tomographic and, thus, volumetric imaging. In this paper, the first tomographic EI XPCi images acquired with a conventional x-ray source at dose levels below that used for preclinical small animal imaging are presented. Methods: Two test objects, a biological sample and a custom-built phantom, were imaged with a laboratory-based EI XPCi setup in tomography mode. Tomographic maps that show the phase shift and attenuating properties of the object were reconstructed, and analyzed in terms of signal-to-noise ratio and quantitative accuracy. Dose measurements using thermoluminescence devices were performed. Results: The obtained images demonstrate that phase based imaging methods can provide superior results compared to attenuation based modalities for weakly attenuating samples also in 3D. Moreover, and, most importantly, they demonstrate the feasibility of low-dose imaging. In addition, the experimental results can be considered quantitative within the constraints imposed by polychromaticity. Conclusions: The results, together with the method's dose efficiency and compatibility with conventional x-ray sources, indicate that tomographic EI XPCi can become an important tool for the routine imaging of biomedical samples.

Clinical experience with Zarzio® in Europe: what have we learned?

Abstract: Biosimilars are similar, but non-identical, versions of existing biological drugs for which patents have expired. Despite the rigorous approval process for biosimilars, concerns have been expressed about the efficacy and safety of these products in clinical practice. Biosimilars of filgrastim, based on the originator product Neupogen®, have been available since 2008 and are now in widespread clinical use in Europe and elsewhere. Three biosimilar G-CSFs have been approved based on a combination of physicochemical and biological protein characterisation, pharmacokinetic and pharmacodynamic assessment in healthy volunteers and efficacy and safety data in patients with cancer. To assess whether biosimilars are effective in the real-world clinical practice setting, a pooled analysis of five post-approval studies of biosimilar G-CSF (Zarzio®) that included 1,302 adult patients who received at least one cycle of chemotherapy with G-CSF support for the prevention of neutropenia was conducted. A total of 36 % of patients had a febrile neutropenia risk of >20 %, while 39.6 % had a risk of 10–20 % based on chemotherapy regimen. The occurrence of severe or febrile neutropenia was within the range of that observed in previous studies of originator G-CSF. In addition, the safety profile of Zarzio® was consistent with that reported for originator G-CSF and the known safety profile of G-CSF. Initial concerns about the use of biosimilars, at least with regard to biosimilar G-CSFs, appear to be unfounded. Adoption of cost-effective biosimilars should help reduce healthcare costs and improve patient access to biological treatments.

Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells.

Abstract: Loss of function of fumarate hydratase (FH), the mitochondrial tumor suppressor and tricarboxylic acid (TCA) cycle enzyme, is associated with a highly malignant form of papillary and collecting duct renal cell cancer. The accumulation of fumarate in these cells has been linked to the tumorigenic process. However, little is known about the overall effects of the loss of FH on cellular metabolism. We performed comprehensive metabolomic analyses of urine from Fh1- deficient mice and stable isotopologue tracing from human and mouse FH-deficient cell lines to investigate the biochemical signature of the loss of FH. The metabolomics analysis revealed that the urea cycle metabolite argininosuccinate is a common metabolic biomarker of FH deficiency. Argininosuccinate was found to be produced from arginine and fumarate by the reverse activity of the urea cycle enzyme argininosuccinate lyase (ASL), making these cells auxotrophic for arginine. Depleting arginine from the growth media by the addition of pegylated arginine deiminase (ADI-PEG 20) decreased the production of argininosuccinate in FH-deficient cells and reduced cell survival and proliferation. These results unravel a previously unidentified correlation between fumarate accumulation and the urea cycle enzyme ASL in FH-deficient cells. The finding that FH-deficient cells become auxotrophic for arginine opens a new therapeutic perspective for the cure of hereditary leiomyomatosis and renal cell cancer (HLRCC).

Pre‐treatment surgical para‐aortic lymph node assessment in locally advanced cervical cancer

Abstract: Background This is an updated version of the original Cochrane review published in The Cochrane Library, Issue 4, 2011. Cervical cancer is the most common cause of death from gynaecological cancers worldwide. Locally advanced cervical cancer, FIGO stage (International Federation of Gynaecology and Obstetrics) equal or more than IB1 is treated with chemotherapy and external beam radiotherapy followed by brachytherapy. If there is metastatic para-aortic nodal disease, radiotherapy is extended to cover this area. Due to increased morbidity, ideally extended-field radiotherapy is given only when para-aortic nodal disease is confirmed. Therefore, accurate assessment of the extent of the disease is very important for planning the most appropriate treatment. Objectives To evaluate the effectiveness and safety of pre-treatment surgical para-aortic lymph node assessment for woman with locally advanced cervical cancer (FIGO stage IB2 to IVA). Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2012, Issue 10), MEDLINE and EMBASE (up to November 2012). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that compared surgical para-aortic lymph node assessment and dissection with radiological staging techniques, in adult women diagnosed with locally advanced cervical cancer. Data collection and analysis Two review authors independently assessed whether potentially relevant trials met the inclusion criteria, abstracted data and assessed risk of bias. One RCT was identified so no meta-analyses were performed. Main results We found only one trial, which included 61 women, that met our inclusion criteria. This trial reported data on surgical versus clinical staging and an assessment of the two surgical staging techniques; laparoscopic (LAP) versus extraperitoneal (EXP) surgical staging. The clinical staging was either a contrast-enhanced computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the abdomen and pelvis to determine nodal status. In this trial, clinical staging appeared to significantly prolong overall and progression-free survival compared to surgical staging. There was no statistically significant difference in the number of women who experienced severe (grade 3 or 4) toxicity. There was no statistically significant difference in the risk of death, disease recurrence or progression, blood loss, severe toxicity and the duration of the operational procedure between LAP and EXP surgical staging techniques. The strength of the evidence is weak in this review as it is based on one small trial that was at moderate risk of bias. Authors' conclusions Since the last version of this review no new studies were found. From the one available RCT we found insufficient evidence that pre-treatment surgical para-aortic lymph node assessment for locally advanced cervical cancer is beneficial, and it may actually have an adverse effect on survival. However, this conclusion is based on analysis of a small single trial and therefore definitive guidance or recommendations for clinical practice cannot be made. Therefore, the decision to offer surgical pre-treatment assessment of para-aortic lymph nodes in locally advanced cervical cancer needs to be individualised. The uncertainty regarding any impact on survival from pre-treatment para-aortic lymph node assessment should be discussed openly with the women.

Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with non‐syndromic phaeochromocytoma, paraganglioma and head and neck paraganglioma

Abstract: OBJECTIVES: Research studies have reported that about a third of individuals with phaeochromocytoma/paraganglioma (PPGL) have an inherited predisposition, although the frequency of specific mutations can vary between populations. We evaluated VHL, SDHB and SDHD mutation testing in cohorts of patients with non-syndromic PPGL and head and neck paraganglioma (HNPGL). DESIGN: Prospective, observational evaluation of NHS practice. PATIENTS: Individuals with PPGL/HNPGL referred to a supraregional genetics testing service over a 10-year period. MEASUREMENTS: Clinical (age, tumour site, malignancy, etc.), mutation frequencies and characteristics. RESULTS: A total of 501 probands with PPGL (n = 413) or HNPGL (n = 88) were studied. Thirty-one percent of patients with PPGL presented had a pathogenic mutation in SDHB, SDHD or VHL. Mutation detection rates were highest in those with a positive family history (62%), malignancy (53%), multiple tumours (33%) or PGL (44%). Twenty-eight percent of individuals with a single sporadic phaeochromocytoma had a mutation. Overall, 63% of patients with HNPGL had a mutation (92% of those with a family history, 89% of those with multicentric tumours and 34% of those with a single sporadic HNPGL). Penetrance was calculated in 121 SDHB mutation-positive probands and 187 of their mutation-positive relatives. Most relatives were asymptomatic and lifetime penetrance in non-proband SDHB mutation carriers was <50%. CONCLUSIONS: Practice-based evaluations of genetic testing in PPGL reveal high mutation detection rates. Although clinical criteria can be used to prioritize mutation testing, mutations were detected in 'low risk groups' indicating a need for comprehensive and inexpensive genetic testing strategies for PPGL and HNPGL.

Risk-reducing surgery increases survival in BRCA1/2 mutation carriers unaffected at time of family referral

Abstract: The aim of this study was to establish if risk-reducing surgery (RRS) increases survival among BRCA1/2 carriers without breast/ovarian cancer at the time of family referral. Female BRCA1/2 carriers were identified from the Manchester Genetic Medicine Database. Those patients alive and unaffected at the date of first family ascertainment were included in this study. Female first-degree relatives (FDRs) without predictive genetic testing who otherwise met eligibility criteria were also included. The effect of breast and ovarian RRS on survival was analysed. The survival experiences of RRS and non-RRS patients, stratified by BRCA status, were examined with Kaplan-Meier curves and contrasted using log-rank tests and Cox models. 691 female BRCA1/2 mutation carriers without breast or ovarian cancer at time of family ascertainment were identified; 346 BRCA1 and 345 BRCA2. 105 BRCA1 carriers and 122 BRCA2 carriers developed breast cancer during follow-up. The hazard of death was statistically significantly lower (P < 0.001) following RRS versus no RRS. 10-year survival for women having RRS was 98.9 % (92.4-99.8 %) among BRCA1 and 98.0 % (92.2-99.5 %) among BRCA2 carriers. This survival benefit with RRS remained significant after FDRs were added. Women who had any form of RRS had increased survival compared to those who did not have RRS; a further increase in survival was seen among women who had both types of surgery. However, formal evidence for a survival advantage from bilateral mastectomy alone requires further research.

Keypad mobile phones are associated with a significant increased risk of microbial contamination compared to touch screen phones

Abstract: The use of mobile phones in the clinical environment by healthcare workers has become widespread. Despite evidence that these devices can harbour pathogenic micro-organisms there is little guidance on how to reduce contamination. Recently touchscreen phones with a single flat surface have been introduced. We hypothesise that bacterial contamination of phones used in hospitals will be lower on touchscreen devices compared to keypad devices. Sixty seven mobile phones belonging to health care workers were sampled. The median colony count for touchscreen phones and keypad devices was 0·09 colony forming units (cfu)/cm2 (interquartile range (IQR) 0.05–0·14) and 0·77 cfu/cm2 (IQR range 0·45–3.52) respectively. Colony counts were significantly higher on the keypad phones (Fisher’s exact test p<0.001). Multivariate analysis showed the type of phone (keypad vs. touch screen) was associated with increased colony counts (F-statistic 14.13: p<0.001). Overall, nine (13%) phones grew either meticillin resistant Staphyl...

A Human Volunteer Study to Identify Variability in Performance in the Cognitive Domain of the Postoperative Quality of Recovery Scale

Abstract: Background: The Postoperative Quality of Recovery Scale found lower than anticipated recovery in the cognitive domain. The definition of cognitive recovery did not allow for performance variability, and may have been too sensitive. This study aimed to examine variability in cognitive performance in volunteers. Methods: One hundred forty-three volunteers completed the cognitive domain questions at baseline, after 15 min and 40 min, and on days 1 and 3. Delivery via face-to-face interview was conducted for the first three measurements,and then randomized for day 1 and 3 measurements (faceto-face only, telephone only, telephone then face-to-face, face-to-face then telephone).

Are the UK oncology trainees adequately informed about the needs of older people with cancer

Abstract: Are the UK oncology trainees adequately informed about the needs of older people with cancer?

A population-level prediction tool for the incidence of first-episode psychosis: translational epidemiology based on cross-sectional data

Abstract: Objectives: Specialist early intervention services (EIS) for people aged 14–35 years with first episodes of psychosis (FEP) have been commissioned throughout England since 2001. A single estimate of population need was used everywhere, but true incidence varies enormously according to sociodemographic factors. We sought to develop a realistically complex, population-based prediction tool for FEP, based on precise estimates of epidemiological risk. Design and participants: Data from 1037 participants in two cross-sectional population-based FEP studies were fitted to several negative binomial regression models to estimate risk coefficients across combinations of different sociodemographic and socioenvironmental factors. We applied these coefficients to the population at-risk of a third, socioeconomically different region to predict expected caseload over 2.5 years, where the observed rates of ICD-10 F10-39 FEP had been concurrently ascertained via EIS. Setting: Empirical population-based epidemiological data from London, Nottingham and Bristol predicted counts in the population at-risk in the East Anglia region of England. Main outcome measures: Observed counts were compared with predicted counts (with 95% prediction intervals (PI)) at EIS and local authority district (LAD) levels in East Anglia to establish the predictive validity of each model. Results: A model with age, sex, ethnicity and population density performed most strongly, predicting 508 FEP participants in EIS in East Anglia (95% PI 459, 559), compared with 522 observed participants. This model predicted correctly in 5/6 EIS and 19/21 LADs. All models performed better than the current gold standard for EIS commissioning in England (716 cases; 95% PI 664–769). Conclusions: We have developed a prediction tool for the incidence of psychotic disorders in England and Wales, made freely available online (http://www.psymaptic.org), to provide healthcare commissioners with accurate forecasts of FEP based on robust epidemiology and anticipated local population need. The initial assessment of some people who do not require subsequent EIS care means additional service resources, not addressed here, will be required.

Photodynamic therapy for retinal capillary hemangioma

Abstract: PURPOSE: To describe the results of photodynamic therapy (PDT) for juxtapapillary and peripheral retinal capillary hemangioma (RCH). PATIENTS AND METHODS: Interventional case series of four eyes (four patients) with juxtapapillary RCH and one eye (one patient) with peripheral RCH. Two eyes with juxtapapillary RCH had received two sessions of full-fluence, double-duration PDT; whereas other two eyes had received single session of half-fluence, single-duration PDT. The peripheral RCH was treated with a single session of full-fluence, single-duration PDT. RESULTS: Two patients had von Hippel-Lindau disease. Follow-up duration ranged from 4 months to 1 year. Pre-PDT visual acuity (VA) ranged from 20/200 to HM (juxtapapillary RCH) and 20/100 (peripheral RCH). Among the eyes with juxtapapillary RCH, tumor regression with partial resolution of macular edema was noted in two eyes (one eye each with half-fluence and full-fluence PDT), whereas two eyes had no change in tumor size with persistent macular edema. VA remained stable in three eyes and declined in one eye. In an eye with peripheral RCH, regression of tumor and macular edema with VA improvement was noted. Post-PDT complications included epiretinal membrane (one eye) and transient exudative retinal detachment (one eye). CONCLUSION: PDT can be effective in reducing macular edema associated with RCH but this does not always correspond with an improvement in VA especially for juxtapapillary tumors.

The use of strontium-90 Beta radiotherapy as adjuvant treatment for conjunctival melanoma.

Abstract: Background/Aims. To report the safety and efficacy of strontium (Sr90) beta radiotherapy as adjuvant treatment for conjunctival melanoma. Methods. A retrospective cohort study was undertaken from 1999 to 2007 of all patients who underwent Sr90 beta radiotherapy for incompletely excised conjunctival melanoma. Failure of treatment was defined as recurrence of a conjunctival melanoma at the same location following beta radiotherapy. Results. Twenty patients underwent Sr90 beta radiotherapy for incompletely excised conjunctival melanoma. Median follow-up interval was 59 months (8–152). All patients had conjunctival melanoma involving the bulbar conjunctiva. Underlying diagnoses included PAM with atypia in 60% (12 of 20), PAM without atypia in 15% (3 of 20), and de novo conjunctival melanoma in 25% (5 of 20). Following Sr90 beta radiotherapy, in 90% (18 out of 20) local control was achieved and visual acuity was not affected in any patient. Three patients (15%) had dry eye symptoms, episcleritis, and descemetcoele, respectively. No cataract or secondary glaucoma was reported. Conclusions. Sr90 treatment is a very effective adjuvant treatment after excisional biopsy and cryotherapy for conjunctival melanoma with a local success rate of 90%. The treatment is not associated with significant side effects and visual acuity is not affected.

The effect of bariatric surgery on echocardiographic indices: a review of the literature.

Abstract: Obesity is the new epidemic and is associated with an increased risk of diastolic and systolic heart failure. Effective treatment options with drastic results such as bariatric surgery have raised interest in the possible reversal of some of the cardiovascular sequelae. Many studies have assessed individually the effect of weight loss on specific echocardiographic indices, mostly employing nonhomogeneous groups. The purpose of this narrative review is to summarise the effect of bariatric surgery on echocardiographic indices of biventricular function and to help in the understanding of the expected echocardiographic changes in bariatric patients after weight-loss surgery

Can we use influencing factors to predict aspiration pneumonia in the United Kingdom

Abstract: The current study builds upon the work of others in looking at influencing factors of aspiration pneumonia in people with a swallowing problem. This study differs from previous researches on this topic, focusing on the United Kingdom (UK) population and involving more recently defined influencing factors of aspiration pneumonia. The study aims to explore the multifactorial nature of aspiration pneumonia in a UKdysphagic client group, as well as different disease specific variables. Speech and Language Therapists collected data on 33 influencing factors over a period of 6 months during routine bedside swallowing assessment of 687 patients. All subjects were adults referred with suspected dysphagia and included acute inpatients, head and neck cancer patients and adults with learning disabilities. The study population included 400 males and 287 females and ages ranged from 17 to 102 giving a mean age of 72.9 years. The influence of the different variables included in the study was evaluated using multivariate logistic regression analysis. The results show that 13 statistically significant influencing factors were implicated in the development of aspiration pneumonia for this group. Out of these, nine correlate with the previous work undertaken in the United States. These were poor mobility, nil by mouth status, age, dependency for feeding, number of medications, Chronic Obstructive Pulmonary Disease (COPD), number of medical conditions, stroke and alcohol abuse. Four further influencing factors were shown to be significant in the UK population, these were dysphagia, only oral intake, bedfast, and male gender. This study confirms that in the UK there are influencing factors in the development of an aspiration pneumonia. It would be prudent to remember that a direct link is yet to be established when applying this knowledge to inform clinical management.

Sequelae and survivorship in patients treated with 131 I-MIBG therapy

Abstract: 131I-meta-iodobenzylguanidine (131I-MIBG) has been in therapeutic use since 1980s. Newer treatment modalities are emerging for neuroendocrine tumours (NETs) and chromaffin cell tumours (CCTs), but many of these do not yet have adequate long-term follow-up to determine their longer term efficacy and sequelae. Fifty-eight patients with metastatic NETs and CCTs who had received 131I-MIBG therapy between 2000 and 2011 were analysed. Survival and any long-term haematological or renal sequelae were investigated. In the NET group, the overall median survival and median survival following the diagnosis of metastatic disease was 124 months. The median survival following the commencement of 131I-MIBG was 66 months. For the CCT group, median survival had not been reached. The 5-year survival from diagnosis and following the diagnosis of metastatic disease was 67% and 67.5% for NETs and CCTs, respectively. The 5-year survival following the commencement of 131I-MIBG therapy was 68%. Thirty-two patients had long-term haematological sequelae: 5 of these 32 patients developed haematological malignancies. Two patients developed a mild deterioration in renal function. Long follow up of 131I-MIBG therapy reveals a noteable rate of bone marrow toxicities and malignancy and long term review of all patients receiving radionuclide therapies is recommended.

Another look at follicular lymphoma: immunophenotypic and molecular analyses identify distinct follicular lymphoma subgroups

Abstract: Aims: The aim of this study was to analyse the immunophenotypic and molecular features of a large series of follicular lymphomas, focusing in particular on atypical cases that fail to express CD10 and/or bcl-2. Such cases present diagnostic pitfalls, especially with regard to the differential diagnosis from follicular hyperplasia and marginal zone B-cell lymphoma. Therefore, we also included an immunohistochemical evaluation of stathmin, which is strongly expressed by germinal centre B cells, as a putative new marker for follicular lymphomas, particularly those with an atypical phenotype. Methods and results: Two hundred and five follicular lymphomas were investigated with immunohistochemistry and fluorescence in-situ hybridization (FISH). The use of three distinct anti-bcl-2 antibodies together with CD10 expression data and FISH analysis for bcl-2 and bcl-6 rearrangements allowed subclassification of follicular lymphoma into four distinct subgroups: (i) CD10-positive/bcl-2-positive, (ii) CD10-positive/bcl-2-negative, (iii) CD10-negative/bcl-2-positive, and (iv) CD10-negative/bcl-2-negative. All cases were bcl-6-positive. STMN1 (stathmin) was shown to be helpful in diagnosing bcl-2-negative and/or CD10-negative follicular lymphomas, and in their distinction from marginal zone B-cell lymphoma. Conclusions: Combined immunohistological and molecular analyses reveal that follicular lymphomas showing an atypical immunophenotypic and molecular profile exist, and we demonstrate that STMN1 represents a novel useful diagnostic marker for these. © 2013 Blackwell Publishing Ltd.

Bone metastases in germ cell tumours: lessons learnt from a large retrospective study.

Abstract: Objective To determine the characteristics of patients with germ cell cancer and bone metastases. Patients and Methods The case records of patients with known germ cell tumours (GCTs) within the Anglian Germ Cell Cancer Group database between January 2005 and March 2011 were reviewed retrospectively. Data were collected for histopathology, presence of bone metastases at diagnosis or relapse, site of bone metastases and imaging method used to confirm bone metastases, treatment received, response to treatment and overall survival. We present here the largest unselected cohort of bone metastases in patients with GCTs. Results In all, 2550 cases of GCTs were reviewed and there was bone involvement in 19 cases. The primary site was either testicular (13/19), mediastinal (1/19) or unknown (5/19). Most cases were non-seminomatous GCTs (11/19, 58%) and only three cases of seminomatous GCTs (3/19, 16%) with five cases in which diagnosis was based on clinical history and significantly raised GCT markers (5/19, 26%). In all of these five cases β-human chorionic gonadotrophin was raised and in three α-fetoprotein was raised, consistent with non-seminomatous GCT. There were bone metastases at diagnosis (0.51%, 13/2550) or at relapse (0.24%, 6/2550). The sites of bone metastases were the vertebrae (15/19, 79%), pelvis (3/19, 16%), ribs (3/19, 16%) and femur (2/19, 11%). Ten patients (53%) had solitary, and nine patients (47%) had multiple, sites of bone metastases. In patients presenting with bone metastases at diagnosis compared with relapse, the mortality rate was 23% (3/13) and 50% (3/6), respectively. After receiving one line of chemotherapy, nine patients (47%) remained in remission not requiring further treatment, six (32%) required further chemotherapy due to subsequent relapse, three (16%) died after first-line chemotherapy and one was lost to follow-up. At the time of data collection and based on the last clinic follow-up, six patients (32%) had died with a median (interquartile range, IQR) follow-up of 11.5 (4.3, 24.8) months and 10 (53%) remained alive with a median (IQR) follow-up of 26 (13.5, 48) months Three patients were lost to follow-up. Of the known patients alive, eight (42%) remained in remission and two (11%) had recurrent disease requiring further treatment. Conclusion Although bone disease in germ cell cancer is rare, awareness of this condition is important and there is a need for prospective evaluation of patient characteristics, treatment approaches and survival outcome in this group of patients.

Choroidal naevi complicated by choroidal neovascular membrane and outer retinal tubulation

Abstract: Aims To present the outcomes of a series of patients with choroidal neovascular membrane (CNV) secondary to a choroidal naevus and report the presence of outer retinal tubulation. Methods In this retrospective series, patients underwent a complete clinical and imaging assessment (fundus photo, fluorescein angiography and optical coherence tomography) and were observed or managed with intravitreal anti-VEGF injections dependent on whether visual acuity was affected. Results Seventeen patients were included in this study. Of this, 46% (8/17) had classic or predominantly classic CNV and 53% (9/17) had occult or minimally classic CNV. Active treatment with intravitreal anti-VEGF injections was required in 35% (6/17). Visual acuity improved in three eyes by 2–4 Snellen lines, remained stable in one eye and worsened in two eyes by 2 Snellen lines. CNV partially regressed in five cases. In the observation group (65%, 11/17), visual acuity did not change during follow-up period. Outer retinal tubulation was found in 18% (3/17). Conclusions Anti-VEGF treatment is effective in the management of vision threatening CNV secondary to a choroidal naevus. Functional or anatomical improvement was obtained in 66% of treated eyes. Outer retinal tubulation, noted in 18%, showed the clinical importance of this sign in determining continuation of anti-VEGF treatment.

A phase III randomized trial of chemoimmunotherapy comprising gemcitabine and capecitabine with or without telomerase vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer.

Abstract: LBA4004 Background: GV1001, a promiscuous class II epitope encompassing aa 611-626 of hTERT led to the development of CD4+ clones recognizing hTERT in patients with advanced pancreatic cancer (APC). Preclinically gemcitabine increases antigen cross-presentation, enhances T cell trafficking/activation, and reduces MDSCs and Tregs. Methods: Patients with APC were randomized 1:1:1 to: Arm 1 GemCap; 2 GemCap for 8/52 followed by GV1001 followed by further GemCap if no PD at week 8; 3 concurrent administration of GemCap and GV1001. 735 (69.2%) had metastatic disease and 948 (89.3%) had ECOG PS=0 or 1. Randomization was stratified by stage and PS. Primary endpoint was overall survival (OS); secondary endpoints included ORR, TTP, and AEs. Recruitment target was 1,110 patients (780 deaths) to permit detection of a hazard ratio of 0.748 between either GV1001 arm and Arm 1 using a 2-sided α=0.025 level of significance with at least 80% power. Results: 1,062 pts from 51 centers were randomized. Trial maturity was hi...

Prostate needle biopsy processing: a survey of laboratory practice across Europe

Abstract: Aim To determine the degree of variation in the handling of prostate needle biopsies (PBNx) in laboratories across Europe. Methods A web based survey was emailed to members of the European Network of Uropathology and the British Association of Urological Pathologists. Results Responses were received from 241 laboratories in 15 countries. PNBx were generally taken by urologists (93.8%) or radiologists (23.7%) but in 8.7% were also taken by non-medical personnel such as radiographers, nurses or biomedical assistants. Of the responding laboratories, 40.8% received cores in separate containers, 42.3% processed one core/block, 54.2% examined three levels/block, 49.4% examined one H&E section/level and 56.1% retained spare sections for potential immunohistochemistry. Of the laboratories, 40.9% retained unstained spares for over a year while 36.2% discarded spares within 1 month of reporting. Only two (0.8%) respondents routinely performed immunohistochemistry on all PNBx. There were differences in laboratory practice between the UK and the rest of Europe (RE). Procurement of PNBx by non-medical personnel was more common in the UK. RE laboratories more commonly received each core in a separate container, processed one core/block, examined fewer levels/block and examined more H&E sections/level. RE laboratories also retained spares for potential immunohistochemistry less often and for shorter periods. Use of p63 as the sole basal cell marker was more common in RE. Conclusions There are marked differences in procurement, handling and processing of PNBx in laboratories across Europe. This data can help the development of best practice guidelines.